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Peripheral blood intermediate monocyte protease-activated receptor-2 expression increases during asthma exacerbations
Nami Shrestha Palikhe1, Vivek Dipak Gandhi2, Yingqi Wu1
1Division of Pulmonary Medicine, Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada; Alberta Respiratory Centre, University of Alberta, Edmonton, Alberta, Canada.
Background:
Myeloid cells, especially dendritic cells and macrophages, play important roles in asthma pathophysiology. Monocytes (Mo) and macrophages express protease-activated receptor-2 (PAR-2), a proinflammatory serine protease receptor implicated in the pathophysiology of allergic airway inflammation. We have revealed that patients with severe asthma and those with a history of frequent asthma exacerbations exhibit increased PAR-2 expression on peripheral blood monocytes.
Objective:
To determine PAR-2 expression on peripheral blood intermediate monocytes (IMMo) in subjects with increased airway inflammation, either as a result of an asthma exacerbation or after an inhalation allergen challenge.
Methods:
A total of 16 adults who presented to the emergency department with asthma exacerbations were recruited after giving an informed consent. After 2 weeks, 10 patients returned for follow-up. A total of 11 patients with mild asthma treated only with as-needed bronchodilators were recruited and underwent inhalation allergen challenge after providing an informed consent. Immune cell profiling was performed by whole blood flow cytometry in both groups of patients.
Results:
PAR-2 expression in peripheral blood IMMo increased in patients with an asthma exacerbation compared with those with stable disease, but this expression decreased after treatment of the asthma exacerbation. Subjects with mild asthma had an increase in percentages of IMMo expressing PAR-2 after an allergen challenge. Patients who presented to the emergency department had lower dendritic cell and dendritic cell subset numbers in peripheral blood during exacerbation compared with after treatment.
Conclusion:
Increased PAR-2 expression on Mo during periods of increased airway inflammation may initiate a positive feedback loop leading to systemic inflammatory changes.
Insights
Protease-activated receptor-2 (PAR-2) expression on monocytes increases during asthma exacerbations and after allergen exposure, suggesting a role in airway inflammation.
Area of Science:
- Immunology
- Allergy and Asthma Research
Background:
- Myeloid cells, including dendritic cells and macrophages, are key players in asthma.
- Protease-activated receptor-2 (PAR-2) on monocytes and macrophages is linked to allergic airway inflammation.
- Increased PAR-2 expression on monocytes is observed in severe asthma and frequent exacerbations.
Purpose of the Study:
- To investigate PAR-2 expression on intermediate monocytes (IMMo) in individuals with heightened airway inflammation.
- To assess PAR-2 levels during asthma exacerbations and post-allergen inhalation.
Main Methods:
- Flow cytometry was used for immune cell profiling in peripheral blood.
- Study included 16 adults with asthma exacerbations and 11 with mild asthma undergoing allergen challenge.
- Monocyte PAR-2 expression was analyzed during exacerbation, post-treatment, and after allergen challenge.
Main Results:
- PAR-2 expression on IMMo rose during asthma exacerbations but decreased post-treatment.
- Mild asthma patients showed increased IMMo PAR-2 expression following allergen inhalation.
- Dendritic cell numbers were reduced in the emergency department group during exacerbation.
Conclusions:
- Elevated PAR-2 on monocytes during inflammation may drive systemic inflammatory feedback loops.
- PAR-2 is implicated in the immune response during acute asthma exacerbations and allergen challenges.
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